Impaired Liver Function
Conditions
Brief summary
This study will evaluate the safety and pharmacokinetics of two doses of orally administered Proellex® in female patients with impaired hepatic function and healthy volunteers with normal hepatic function.
Detailed description
16 subjects will be allocated to 2 groups. The test group will consist of 8 female patients with moderately impaired hepatic function meeting the Child-Pugh Class B severity criteria, while the control group will consist of 8 healthy female adult volunteers. During Stage I, all subjects will receive a single oral dose of 25mg of Proellex® (fasting state) and be followed in a Clinical Research Unit (CRU) for about three days. Only subjects who do not experience serious adverse events (SAEs) or adverse events (AEs) that are determined by Investigator to be possibly, probably or definitely related to the treatment will participate in Stage II. The dose will be increased to a single dose of 50mg of Proellex® (fasting state) and subjects will be followed in a Clinical Research Unit (CRU) for about three days. Subjects will undergo blood draws at several time points.
Interventions
DRUGProellex
Proellex 25 mg capsule, single dose
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 62 Years
Healthy volunteers
Yes
Inclusion criteria
* Speak, read, and understand English or Spanish and is willing and able to provide written informed consent on an IRB-approved form prior to the initiation of any study procedures; * Female, between the ages of 18 and 48 years with Body Mass Index (BMI) between 18 and 39, inclusive, are preferred; however, subjects up to 62 years old, inclusive, may participate; * Subjects with moderate hepatic insufficiency must meet the Class B level of the Child-Pugh criteria; * Subjects must have evidence of stable hepatic impairment; * If on medications for treatment of the complications of liver disease, and other concomitant chronic illnesses, subjects must have been taking the medications at a stable dose for at least 10 days prior to the first dosing date and are then to be continued at the same dose for the duration of the study; * Non-smokers are preferred, but light to moderate smoking will be allowed (no more than 10 cigarettes/day) * Subject is willing to remain in the clinic for the screening visit and for two treatment visits (approximately 3 days for each treatment visit); * Other inclusion criteria may apply
Exclusion criteria
* Past or present history of an allergic reaction to the formulations administered in this study, or in the opinion of the Investigator, suggesting an increased potential for an adverse hypersensitivity; * Pregnant or lactating females, or women who are attempting or expecting to become pregnant at any time during the study or one month after the study; * A physical illness within three (3) months of the study that would interfere with the study as determined by the Investigator; * An acute illness within five (5) days of study medication administration; * Positive urine drug screen at the screening visit based on laboratory testing; * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Blood Concentration (Cmax) | 48 hours | Cmax of a single dose of 25mg and 50mg of Proellex® in female patients with impaired hepatic function and in volunteers with normal hepatic function, assessed from samples collected at: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 12, 16, 20, 24, 32, 36, 40 and 48 hours post dose.. |
| Proellex Half-life (T1/2) | 48 hours | Time for Proellex concentration to decrease by half (T1/2) of a single dose of 25mg and 50mg of Proellex® in female patients with impaired hepatic function and in volunteers with normal hepatic function,measured from samples collected at: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 12, 16, 20, 24, 32, 36, 40 and 48 hours post dose.. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC0-t) for Proellex | 48 hours | AUC0-t of a single dose of 25mg and 50mg of Proellex® in female patients with impaired hepatic function and in volunteers with normal hepatic function, measured from samples collected at: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 12, 16, 20, 24, 32, 36, 40 and 48 hours post dose. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Healthy females | 8 |
| Mpaired Hepatically impaired females | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Healthy | Mpaired | Total |
|---|---|---|---|
| Age, Continuous | 41.4 years STANDARD_DEVIATION 4.1 | 54.1 years STANDARD_DEVIATION 4.8 | 47.8 years STANDARD_DEVIATION 7.9 |
| Region of Enrollment United States | 8 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Maximum Blood Concentration (Cmax)
Cmax of a single dose of 25mg and 50mg of Proellex® in female patients with impaired hepatic function and in volunteers with normal hepatic function, assessed from samples collected at: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 12, 16, 20, 24, 32, 36, 40 and 48 hours post dose..
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Proellex 25 mg Healthy | Maximum Blood Concentration (Cmax) | 827.5 ng/L | Standard Deviation 312.9 |
| Proellex 25 mg Impaired | Maximum Blood Concentration (Cmax) | 587.6 ng/L | Standard Deviation 261.3 |
| Proellex 50 mg Healthy | Maximum Blood Concentration (Cmax) | 1589.5 ng/L | Standard Deviation 482.3 |
| Proellex 50 mg Impaired | Maximum Blood Concentration (Cmax) | 974.0 ng/L | Standard Deviation 400.2 |
Primary
Proellex Half-life (T1/2)
Time for Proellex concentration to decrease by half (T1/2) of a single dose of 25mg and 50mg of Proellex® in female patients with impaired hepatic function and in volunteers with normal hepatic function,measured from samples collected at: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 12, 16, 20, 24, 32, 36, 40 and 48 hours post dose..
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Proellex 25 mg Healthy | Proellex Half-life (T1/2) | 24.5 Hours | Standard Deviation 8.4 |
| Proellex 25 mg Impaired | Proellex Half-life (T1/2) | 37.9 Hours | Standard Deviation 18.9 |
| Proellex 50 mg Healthy | Proellex Half-life (T1/2) | 24.2 Hours | Standard Deviation 10.1 |
| Proellex 50 mg Impaired | Proellex Half-life (T1/2) | 30.9 Hours | Standard Deviation 10.8 |
Secondary
Area Under the Curve (AUC0-t) for Proellex
AUC0-t of a single dose of 25mg and 50mg of Proellex® in female patients with impaired hepatic function and in volunteers with normal hepatic function, measured from samples collected at: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 7, 9, 12, 16, 20, 24, 32, 36, 40 and 48 hours post dose.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Proellex 25 mg Healthy | Area Under the Curve (AUC0-t) for Proellex | 5147.2 ng x min/L | Standard Deviation 2647.3 |
| Proellex 25 mg Impaired | Area Under the Curve (AUC0-t) for Proellex | 3603.1 ng x min/L | Standard Deviation 1777.2 |
| Proellex 50 mg Healthy | Area Under the Curve (AUC0-t) for Proellex | 9062.4 ng x min/L | Standard Deviation 4616.1 |
| Proellex 50 mg Impaired | Area Under the Curve (AUC0-t) for Proellex | 6988.6 ng x min/L | Standard Deviation 3289.1 |